A visual review….

A visual review….
A visual review….
Cytokines:
• Mediators

• “low” molecular weight proteins

• Less than 30 kDa

• Can be classified by recurrent architecture

Functional features
• Potent
– Some function at 10-15 Molar

• Local
– autocrine
– paracrine
– (sometimes) endocrine

• Highly interactive
– pleiotropic
– redundant
– synergistic / antagonistic
Functional features
• Potent
– Some
function at
10-15 Molar
Functional features
• Local
– autocrine
– paracrine
– (sometimes)
endocrine
Functional features
• Highly interactive

pleiotropic

redundant

synergistic

antagonistic
Cytokine families
I. Hematopoietic family
II. Interferon family
III. Tumor necrosis factor family
IV. Chemokine family

I, II, and III elicit physiological responses.

IV serves as a chemoattractant.
Hematopoietic family
Defined by architecture…
Interferon family….
http://www.hon.ch/Library/Theme/Allergy/Glossary/i
fn.html

http://www.ncbi.nlm.nih.gov/mapview/map_search.c
gi?chr=hum_chr.inf&query=Interferon&qchr=&strai
n=&neighb=off&advsrch=off

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id
=147570
Tumor necrosis factor…

• Time to be critical…
• Question: What does the text say?
• Answer: Not a lot.
– More specifically, there is no text.
– There is an entry in Table 12.1 (which
stretches over four pages!) What does it
say?
– “Has toxic effects. Induces cytokine
secretion…”
 So, something’s amiss…
• Try another approach.
• Cytokines are soluble immunomodulators.
• That means that they are ligands.
• Question: Can they be characterized in
terms of their receptors?
• Answer: Yes.
The receptor families:
Of receptors and signal transduction…
• Receptors for cytokines have surface
component, single transmembrane
component, and cytoplasmic tails.

• Commonly multimeric. The protomers

can associate in different groupings; the
various associations have different
affinities for cytokines; hence, different
intensities of signaling.

• The different protomers also have

different signaling functions, e. g.
phosphorylation sites.
What are the principal signaling systems?

JAK’s
&
STAT’s
OK, let’s look at a complex image
And, an important example…
And, an update…
Some terms (from Horst Ibelgaufts):
cytokine network (aka: Neuroimmune network ).

“This is, of course, true to the extreme: connect

everything with everything in a diagram of
100 cell types and 500 factors -and add some
extra lines.”

Synonyms:Horst Ibelgaufts'COPE: Cytokines Online Pathfinder Encyclopaedia

zoo of factors
jungle of interactions
deep morasses of acronyms
bleak deserts of synonyms